Teichoic acid biosynthesis

If the primary mechanism of daptomycin bactericidal activity is dissipation of membrane function that indirectly influences peptidoglycan, C A, RHA, protein, lipid, and teichoic acid biosynthesis, it is not clear why daptomycin is synergistic with aminoglycosides. Uptake and bactericidal activity of aminoglycosides require membrane potential (72,73). 

The mechanism for the polymerization of the teichoic acids has not been definitively established, but it is most probably very similar to the biosyntheses of the other lipid-coenzyme-dependent polysaccharides, the peptidomurein and Salmonella 0-antigen polysaccharide, in which the monomer unit or repeating unit attached to the lipid polyprenol pyrophosphate carrier is inserted between the growing chain and the lipid coenzyme carrier. See Fig. 10.12B for the proposed mechanism for teichoic acid biosynthesis. 

Cyclic acetals of pyruvic acid are common in extracellular polysaccharides (compare, for example, Ref. 6). They have also been found in some LPS, namely, those from Shigella dysenteriae type 6 and E. coli 0-149 (Ref. 139), and in the teichoic acid from Brevibacterium iodinum. The biosynthesis of these acetals has already been discussed. 

The incorporation of the D-alanine ester groups is, presumably, the last stage in the biosynthesis of teichoic acids. Several organisms possess enzymes which activate D-alanine, that is, which form a D-alanyl-adenosine 5-phosphate-enzyme complex but, so far, there has been no demonstration of incorporation, in cell-free systems, of D-alanine into teichoic acid or any... 

In the present review, we briefly describe the structures, functions and biosynthesis of teichoic acids. Then the chemical syntheses of TAs and fragments of the polymer chains are described in more detail. 

Park and Strominger noticed the accumulation of a C3didine derivative in cultures of Staphylococcus aureus which had been inhibited by chloramphenicol, penicillin, or Crystal Violet. This cytidine derivative has been identified by Baddiley s group as cytidine ribitol pyrophosphate. Since these inhibitors affect the cell-wall synthesis, the data lend support to the belief that the cytidine compound is involved in the biosynthesis of a cell-wall constituent, and a likely candidate would be ribitol teichoic acid. 

The biosynthesis of the teichoic acid of Staphylococcus aureus (Copenhagen) has been studied by Nathenson and Strominger. This polysaccharide is composed of ribitol units linked to each other by 1,5-phosphate diester bridges. 2-Acetamido-2-deoxy-n-glucopyranosyl residues are joined to the ribitol residues, 85% in a-D-linkages and 15% in S-D-linkages. The polymer also contains n-alanine, esterified to the ribitol. 

Glaser and Burger studied the biosynthesis of teichoic acids with particulate preparations from Bacillus licheniformis (ATGC 9945) and B. subtilis (NCTG 3610). They found that these preparations catalyze the synthesis of poly(glycerol phosphate) according to the reaction... 

Archibald, A.R. (1974) The structure, biosynthesis and function of teichoic acid. Advances in Microbiology and Physiology 11,53-95. 

Ward, J.B. (1981). Teichoic and Teichuronic Acids Biosynthesis, Assembly and Location . Microbiological Reviews, 45, 211-243. 

The glycosyl phosphopolyprenols (10.63) are usually classed as a type of glycolipid since they are formed as intermediates in the biosynthesis of teichoic acids and bacterial lipopolysaccharides. 

Canepari et al. (74) have shown that at the MIC, daptomycin caused only partial blockage of DNA, RNA, protein, and peptidoglycan biosynthesis in . faecium. In contrast, it caused >50% inhibition of radiolabeled phosphate into teichoic acid and >90% inhibition of incorporation of radiolabeled glycerol into lipoteichoic acid in 20 min in both S. aureus and in . faecium. They also showed that daptomycin does not penetrate bacterial cells, but binds reversibly to cell walls and irreversibly to cell membrane in the... 

Teichoic Acids.—Recent reviews have referred to the occurrence and functions of membrane teichoic acids, the biosynthesis of bacterial cell walls and of teichoic acids in bacterial cell walls and membranes, and the surface carbohydrates of prokaryotic cells. ... 

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